Incidence and Risk Factors for Pneumonitis Associated with Immune Checkpoint Inhibitors in Advanced-Stage Non-Small Cell Lung Cancer: A Single Center Experience.

e15089 Background: Conventional treatments for advanced-stage non-small cell lung cancer (NSCLC) confer a progression-free survival of only about 6 months. Immune checkpoint inhibitors (ICIs) have become standard therapies in the management of advanced NSCLC, but are associated with a variety of immune-related adverse events that may be dose-limiting (irAEs). Risk factors for ICI-related pneumonitis, a potentially fatal irAE, have not been well established. We sought to determine the incidence and risk factors for ICI-related pneumonitis in NSCLC in a cohort of patients treated with ICIs as standard of care or as part of a clinical trial. Methods: We performed a retrospective review of 525 patients with advanced NSCLC who received ICI therapy with PD-1 inhibitors, with or without CTLA-4 inhibitors, at MD Anderson Cancer Center between 2015 and 2018. Patients with incomplete data were excluded from the study. Clinical data was collected at the time of ICI therapy and at the time of irAE. The diagnosis of pneumonitis was based on clinical presentation, imaging findings, and microbiological results. We constructed a Fine-Gray competing risks regression model with pneumonitis as the outcome of interest and all-cause mortality as the competing risk. Results: In our initial data analysis based on available data shows a 9.7% raw incidence of pneumonitis (17/177). We found no association between age, race, gender, type of anti-PD-1 therapy, concurrent use of CTLA-4 inhibitors, tumor histology, cumulative radiation dose, or smoking pack-years with the risk for pneumonitis. Patients who were therapy-naïve at the initiation of ICI therapy (hazard ratio [HR] 3.3, 95% confidence interval [CI] 1.0-10.6, p = 0.04), and patients with prior lung disease (HR 2.7, 95% CI 0.8-8.5, p = 0.1) had around a three-fold increase in the risk for pneumonitis after accounting for the competing risk of mortality. Conclusions: NSCLC patients who are therapy-naïve or have prior lung disease on initiation of ICI therapy have a higher risk for pneumonitis. Other studies have shown an increase in pneumonitis in therapy-naïve patients, but the association with prior lung disease is novel. Further analysis on this cohort is ongoing.